Dicyclohexylcarbodiimide → HCID 178452632, compound

HRID 1284447Notes

Reaction equation

HRID 1284447 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:10]=2)[CH2:5][C@@H:4]([C:20](O)=[O:21])[NH:3]1.ON1C(=O)CCC1=O.C1CCC(N=C=NC2CCCCC2)CC1.[NH2:46][C@H:47]([C:54]([N:56]1[CH2:63][CH2:62][CH2:61][C@H:57]1[C:58]([NH2:60])=[O:59])=[O:55])[CH2:48][C:49]1[N:53]=[CH:52][NH:51][CH:50]=1>C(N(CC)CC)C.CN(C=O)C>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([NH:12][C:13]([O:15][C:16]([CH3:18])([CH3:19])[CH3:17])=[O:14])[CH:10]=2)[CH2:5][C@@H:4]([C:20]([NH:46][C@H:47]([C:54]([N:56]2[CH2:63][CH2:62][CH2:61][C@H:57]2[C:58]([NH2:60])=[O:59])=[O:55])[CH2:48][C:49]2[N:53]=[CH:52][NH:51][CH:50]=2)=[O:21])[NH:3]1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 13935805HCID 13935805, compoundHCID 178513962HCID 178513962, compound

Product 1

HCID 178452632HCID 178452632, compoundYield 33.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of (3S)-1-oxo-7-tert.-butyloxycarbonylamino-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (680 mg), N-hydroxysuccinimide (280 mg), DCC (500 mg) and DMF (7 ml) is stirred for 1.5 hours. L-Histidyl-L-prolinamide.2HBr (990 mg) and triethylamine (1 ml) are added to the mixture. The mixture is stirred for 2 days. Insoluble materials are filtered off, and the filtrate is distilled under reduced pressure to remove DMF. The residue is dissolved in 20% citric acid, and washed with chloroform. The washed solution is adjusted to pH 9, and the solution is passed through a column (2.6×20 cm) packed with CHP-20P resin. The column is washed with water (one liter) and 30% methanol (1.5 liter) successively, and then the product is eluted with 50% methanol. The fraction positive to Pauly reagent are collected, and the collected solution is lyophilized, whereby Nα -[(3S)-1-oxo-7-tert.-butyloxycarbonylamino-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]-L-histidyl-L-prolinamide (400 mg) is obtained. Yield: 33.3%.

Workup

  1. stirringThe mixture is stirred for 2 days
  2. filtrationInsoluble materials are filtered off
  3. distillationthe filtrate is distilled under reduced pressure
  4. customto remove DMF
  5. dissolutionThe residue is dissolved in 20% citric acid
  6. washwashed with chloroform
  7. washThe column is washed with water (one liter) and 30% methanol (1.5 liter) successively
  8. washthe product is eluted with 50% methanol
  9. customThe fraction positive to Pauly reagent are collected

Sources & evidence

ORD record
ord-9797256877f244b69bfe8486b78fde05
Source dataset
uspto-grants-1986_01
Patent number
US04563306

Reaction notes

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